Mechanism of novel vitamin K analog induced growth inhibition in human hepatoma cell line.
BACKGROUND/AIMS: To understand the mechanisms of liver regeneration or hepatoma apoptosis, it is important to estimate the turning point of the signal transduction by growth factor receptor. Since 2-(2-hydroxyethylsulfaryl) 3-methyl-1,4-naphthoquinone or CPD 5 has been shown to mediate the phosphorylation of epidermal growth factor (EGF) receptor in Hep3B hepatoma cells, the differences between EGF and CPD 5-mediated signal transduction were studied. METHODS: DNA content was measured by Hoechst fluorescent assay. Phosphorylated proteins were described with Western blots or two-dimensional electrophoresis. RESULTS: CPD 5- induced EGFR phosphorylation was functional to stimulate Ras pathway. However, CPD 5- mediated extracellular signal-regulated kinase ( ERK) phosphorylation was not antagonized by inhibition of upstream activation with PD153035. CPD 5 inhibited ERK dephosphorylation in cell lysate, suggesting that ERK phosphorylation by CPD 5 was depending on kinase activity and phosphatase inhibition. Two-dimensional electrophoresis showed extra phospho ERK spot, which was indicated to have close association with CPD 5-induced growth inhibition, since U0126 antagonized growth inhibition and appearance of this spot. CONCLUSIONS: The turning point of EGFR pathway was proved to have close association with the expressed level of phosphorylated ERK. ERK phosphorylation was suggested to play a critical role in growth factor-induced signal transduction.[1]References
- Mechanism of novel vitamin K analog induced growth inhibition in human hepatoma cell line. Osada, S., Carr, B.I. J. Hepatol. (2001) [Pubmed]
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